In this work we intend to purify and characterize the twisted tubules which make up the neurofibrillary bundles in Alzheimer's Disease and to compare them to the normally occurring neurofilaments and neurotubules. We shall compare the protein electrophoretic profiles of cellular and subcellular fractions from Alzheimer's disease, senile dementia with neurofibrillary change, the Guam Parkinsonism Dementia Complex and mongolism with neurofibrillary change. The chemistry of the subunit of the axonal neurofilament will be characterized chemically and compared to the subunits of the microtubule using peptide mapping techniques. The role of GTP and calcium on the assembly of tubulin into microtubules will be investigated with particular attention devoted to the role that phosphate transfer might have in the assembly process. The solution conformation of the tubulin molecule on interaction with GTP and colchicine will be determined and the changes which occur on assembly into microtubules assessed. Specific groups on the protein will be modified chemically to see if some idea of the sites involved in assembly might be obtained. Studies are to be undertaken to see if a protein analogous to ciliary ATPase Dynein exists in brain. The synthesis, turnover and quantities of tubulin, actin, myosin and the neurofilament proteins in clonal neuroblastoma lines which differ in their abilities to form neurites will be investigated with an eye toward determining the way in which they may play a role in neuronal morphogenesis. The cerebellar outflow degeneration mutant (COD) will be used to assess the fate of the fibrous proteins in a state where "programmed" axonal destruction occurs.